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Effect of Cordycepin-Enriched WIB801C from Cordyceps militaris Suppressing Fibrinogen Binding to Glycoprotein IIb/IIIa

  • Lee, Dong-Ha (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University) ;
  • Kim, Hyun-Hong (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University) ;
  • Lim, Deok Hwi (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University) ;
  • Kim, Jong-Lae (Natural Product Research Team, Central Research Center, Whanin Pharm. Co., Ltd.) ;
  • Park, Hwa-Jin (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University)
  • Received : 2014.07.20
  • Accepted : 2014.11.04
  • Published : 2015.01.01

Abstract

In this study, we investigated the effects of cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha on collagen-stimulated platelet aggregation. CE-WIB801C dose dependently inhibited collagen-induced platelet aggregation, and had a synergistic effect together with cordycepin (W-cordycepin) from CE-WIB801C on the inhibition of collagen-induced platelet aggregation. CE-WIB801C and cordycepin stimulated the phosphorylation of VASP ($Ser^{157}$) and the dephosphorylation of PI3K and Akt, and inhibited the binding of fibrinogen to glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}3$) and the release of ATP and serotonin in collagen-induced platelet aggregation. A-kinase inhibitor Rp-8-Br-cAMPS reduced CE-WIB801C-, and cordycepin-increased VASP ($Ser^{157}$) phosphorylation, and increased CE-WIB801C-, and cordycepin-inhibited the fibrinogen binding to ${\alpha}IIb/{\beta}3$. Therefore, we demonstrate that CE-WIB801C-, and cordycepin-inhibited fibrinogen binding to ${\alpha}IIb/{\beta}3$are due to stimulation of cAMP-dependent phosphorylation of VASP ($Ser^{157}$), and inhibition of PI3K/Akt phosphorylation. These results strongly indicate that CE-WIB801C and cordycepin may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

Keywords

References

  1. Barragan, P., Bouvier, J. L., Roquebert, P. O., Macaluso, G., Commeau, P., Comet, B., Lafont, A., Camoin, L., Walter, U. and Eigenthaler, M. (2003) Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation. Catheter. Cardiovasc. Interv. 59, 295-302. https://doi.org/10.1002/ccd.10497
  2. Castro-Malaspina, H., Rabellino, E. M., Yen, A., Nachman, R. L. and Moore, M. A. (1981) Human megakaryocyte stimulation of proliferation of bone marrow fibroblasts. Blood 57, 781-787.
  3. Chen, J., De, S., Damron, D. S., Chen, W. S., Hay, N. and Byzova, T. V. (2004) Impaired platelet responses to thrombin and collagen in AKT-1-deficient mice. Blood 104, 1703-1710. https://doi.org/10.1182/blood-2003-10-3428
  4. Cho, H. J., Cho, J. Y., Rhee, M. H., Lim, C. R., and Park, H. J. (2006) Cordycepin (3'-deoxyadenosine) inhibits human platelet aggregation induced by U46619, a TXA2 analogue. J. Pharm. Pharmacol. 58, 1677-1682. https://doi.org/10.1211/jpp.58.12.0016
  5. Cho, H. J., Cho, J. Y., Rhee, M. H. and Park, H. J. (2007a) Cordycepin (3'-deoxyadenosine) inhibits human platelet aggregation in a cyclic AMP- and cyclic GMP-dependent manner. Eur. J. Pharmacol. 558, 43-51. https://doi.org/10.1016/j.ejphar.2006.11.073
  6. Cho, H. J., Cho J. Y., Rhee, M. H., Kim, H. S., Lee, H. S., and Park, H. J. (2007b) Inhibitory effects of cordycepin (3'-deoxyadenosine), a component of Cordyceps militaris, on human platelet aggregation induced by thapsigargin. J. Microbiol. Biotechnol. 17, 1134-1138.
  7. Clutton, P., Folts, J. D. and Freedman, J. E. (2001) Pharmacological control of platelet function. Pharmacol. Res. 44, 255-264. https://doi.org/10.1006/phrs.2001.0861
  8. Eigenthaler, M., Nolte, C., Halbrugge, M. and Walter U. (1992) Concentration and regulation of cyclic nucleotides, cyclic-nucleotidedependent protein kinases and one of their major substrates in human platelets. Estimating the rate of cAMP-regulated and cGMP-regulated protein phosphorylation in intact cells. Eur. J. Biochem. 205, 471-481. https://doi.org/10.1111/j.1432-1033.1992.tb16803.x
  9. Gambaryan, S., Kobsar, A., Rukoyatkina, N., Herterich, S., Geiger, J., Smolenski, A., Lohmann, S. M. and Walter, U. (2010) Thrombin and collagen induce a feedback inhibitory signaling pathway in platelets involving dissociation of the catalytic subunit of protein kinase A from an NFkappaB-IkappaB complex. J. Biol. Chem. 285, 18352-18363. https://doi.org/10.1074/jbc.M109.077602
  10. Hayashi, H. and Sudo, T. (2009) Effects of the cAMP-elevating agents cilostamide, cilostazol and forskolin on the phosphorylation of Akt and GSK-3beta in platelets. Thromb. Haemost. 102, 327-335.
  11. Holash, J., Maisonpierre, P. C., Compton, D., Boland, P., Alexander, C. R., Zagzag, D., Yancopoulos, G. D. and Wiegand, S. J. (1999) Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 284, 1994-1998. https://doi.org/10.1126/science.284.5422.1994
  12. Horstrup, K., Jablonka, B., Honig-Liedl, P., Just, M., Kochsiek, K. and Walter, U. (1994) Phosphorylation of focal adhesion vasodilatorstimulated phosphoprotein at Ser157 in intact human platelets correlates with fibrinogen receptor inhibition. Eur. J. Biochem. 225, 21-27. https://doi.org/10.1111/j.1432-1033.1994.00021.x
  13. Jennings, L. K. (2009) Role of platelets in atherothrombosis. Am. J. Cardiol. 103, 4A-10A. https://doi.org/10.1016/S0002-9149(09)00558-X
  14. Kaibuchi, K., Sano, K., Hoshijima, M., Takai, Y. and Nishizuka, Y. (1982) Phosphatidylinositol turnover in platelet activation; calcium mobilization and protein phosphorylation. Cell Calcium 3, 323-335. https://doi.org/10.1016/0143-4160(82)90020-3
  15. Kamruzzaman, S. M., Yayeh, T., Ji, H. D., Park, J.Y., Kwon, Y. S., Lee, I. K., Kim, S., Oh, S. H., Kim, S. D., Roh, S. S., Yun, B. S. and Rhee, M. H. (2013) p-Terphenyl curtisian E inhibits in vitro platelet aggregation via cAMP elevation and VASP phosphorylation. Vascul. Pharmacol. 59, 83-89. https://doi.org/10.1016/j.vph.2013.07.002
  16. Kim, H. G., Shrestha, B., Lim, S. Y., Yoon, D. H., Chang, W. C., Shin, D. J., Han, S. K., Park, S. M., Park, J. H., Park, H. I., Sung, J. M., Jang, Y., Chung, N., Hwang, K. C. and Kim, T. W. (2006) Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-kappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells. Eur. J. Pharmacol. 545, 192-199. https://doi.org/10.1016/j.ejphar.2006.06.047
  17. Laurent, V., Loisel, T. P., Harbeck, B., Wehman, A., Grobe, L., Jockusch, B. M., Wehland, J., Gertler, F. B. and Carlier, M. (1999) Role of proteins of the Ena/VASP family in actin-based motility of Listeria monocytogenes. J. Cell Biol. 144, 1245-1258. https://doi.org/10.1083/jcb.144.6.1245
  18. Lee, D. H., Kim, H. H., Cho, H.J., Bae, J. S., Yu, Y. B. and Park, H. J. (2014a) Antiplatelet effects of caffeic acid due to $Ca^{2+}$ mobilizationinhibition via cAMP-dependent inositol-1, 4, 5-trisphosphate receptor phosphorylation. J. Atheroscler. Thromb. 21, 23-37.
  19. Lee, D. H., Kim, H. H., Cho, H. J., Yu, Y. B., Kang, H. C., Kim, J. L., Lee, J. J. and Park, H. J. (2014b) Cordycepin-Enriched WIB801C from Cordyceps militaris inhibits collagen-induced [$Ca^{2+}$]i mobilization via cAMP-dependent phosphorylation of inositol 1, 4, 5-trisphosphate receptor in human platelets. Biomol. Ther. 22, 223-231. https://doi.org/10.4062/biomolther.2014.025
  20. Lee, D. H., Kwon, H. W., Kim, H. H., Lim, D. H., Nam, G. S., Shin, J. H., Kim, Y. Y., Kim, J. L., Lee, J. J., Kwon, H. K. and Park, H. J. (2014c) Cordycepin-enriched WIB801C from Cordyceps militaris inhibits ADP-induced [$Ca^{2+}$]i mobilization and fibrinogen binding via phosphorylation of IP3R and VASP. Arch. Pharm. Res. DOI 10.1007/ s12272-014-0436-z. [Epub ahead of print]
  21. Li, Z., Ajdic, J., Eigenthaler, M. and Du, X. (2003) A predominant role for cAMP-dependent protein kinase in the cGMP-induced phosphorylation of vasodilator-stimulated phosphoprotein and platelet inhibition in humans. Blood 101, 4423-4429. https://doi.org/10.1182/blood-2002-10-3210
  22. Lincoff, A. M., Califf, R. M. and Topol, E. J. (2000) Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease. J. Am. Coll. Cardiol. 35, 1103-1115. https://doi.org/10.1016/S0735-1097(00)00554-4
  23. Michal, F. and Motamed, M. (1976) Shape change and aggregation of blood platelets: interaction between the effects of adenosine and diphosphate, 5-hydroxytryptamine and adrenaline. Br. J. Pharmacol. 56, 209-218. https://doi.org/10.1111/j.1476-5381.1976.tb07444.x
  24. Morello, F., Perino, A. and Hirsch, E. (2009) Phosphoinositide 3-kinase signalling in the vascular system. Cardiovasc. Res. 82, 261-271.
  25. Nagai, R., Suzuki, T., Aizawa, K., Shindo, T. and Manabe, I. (2005) Significance of the transcription factor KLF5 in cardiovascular remodeling. J. Thromb. Haemost. 3, 1569-1576. https://doi.org/10.1111/j.1538-7836.2005.01366.x
  26. Nishikawa, M., Tanaka, T. and Hidaka, H. (1980) $Ca^{2+}$-calmodulindependent phosphorylation and platelet secretion. Nature 287, 863-865. https://doi.org/10.1038/287863a0
  27. Ok, W. J., Cho, H. J., Kim, H. H., Lee, D. H., Kang, H. Y., Kwon, H. W., Rhee, M. H., Kim, M. and Park, H. J. (2012) Epigallocatechin-3- gallate has an anti-platelet effect in a cyclic AMP-dependent manner. J. Atheroscler. Thromb. 19, 337-348. https://doi.org/10.5551/jat.10363
  28. Packham, M. A. and Mustard, J. F. (1986) The role of platelets in the development and complications of atherosclerosis. Semin. Hematol. 23, 8-26.
  29. Payrastre, B., Missy, K., Trumel, C., Bodin, S., Plantavid, M. and Chap, H. (2000) The integrin alpha IIb/beta 3 in human platelet signal transduction. Biochem. Pharmacol. 60, 1069-1074. https://doi.org/10.1016/S0006-2952(00)00417-2
  30. Phillips, D. R., Nannizzi-Alaimo, L. and Prasad K.S. (2001) ${\beta}_{3}$ tyrosine phosphorylation in ${\alpha}IIb/{\beta}_{3}$ (platelet membrane GP IIb-IIIa) outsidein integrin signaling. Thromb. Haemost. 86, 246-58.
  31. Phillips, D. R., Conley, P. B., Sinha, U. and Andre, P. (2005) Therapeutic approaches in arterial thrombosis. J. Thromb. Haemost. 3, 1577-1589. https://doi.org/10.1111/j.1538-7836.2005.01418.x
  32. Sabatine, M. S. and Jang, I. K. (2000) The use of glycoprotein IIb/ IIIa inhibitors in patients with coronary artery disease. Am. J. Med. 109, 224-237. https://doi.org/10.1016/S0002-9343(00)00474-5
  33. Schwartz, S. M. and Ross, R. (1984) Cellular proliferation in atherosclerosis and hypertension. Prog. Cardiovasc. Dis. 26, 355-372. https://doi.org/10.1016/0033-0620(84)90010-0
  34. Schwartz, S. M. and Reidy, M.A. (1987) Common mechanisms of proliferation of smooth muscle in atherosclerosis and hypertension. Hum. Pathol. 18, 240-247. https://doi.org/10.1016/S0046-8177(87)80006-0
  35. Schwartz, S. M., Heinmark, R. L. and Majesky, M. W. (1990) Developmental mechanisms underlying pathology of arteries. Physiol. Rev. 70, 1177-1209. https://doi.org/10.1152/physrev.1990.70.4.1177
  36. Seppa, H., Grotendorst, G., Seppa, S., Schiffmann, E. and Martin, G. R. (1982) Platelet-derived growth factor in chemotactic for fibroblasts. J. Cell Biol. 92, 584-588. https://doi.org/10.1083/jcb.92.2.584
  37. Shattil, S. J. and Newman, P. J. (2004) Integrins: dynamic scaffolds for adhesion and signaling in platelets. Blood. 104, 1606-1615. https://doi.org/10.1182/blood-2004-04-1257
  38. Smolenski, A., Bachmann, C., Reinhard, K., Honig-Liedl, P., Jarchau, T., Hoschuetzky, H. and Walter U. (1998) Analysis and regulation of vasodilator-stimulated phosphoprotein serine 239 phosphorylation in vitro and in intact cells using a phosphospecific monoclonal antibody. J. Biol. Chem. 273, 20029-20035. https://doi.org/10.1074/jbc.273.32.20029
  39. Sudo, T., Ito, H. and Kimura, Y. (2003) Phosphorylation of the vasodilator- stimulated phosphoprotein (VASP) by the anti-platelet drug, cilostazol, in platelets. Platelets 14, 381-390. https://doi.org/10.1080/09537100310001598819
  40. van Willigen, G. and Akkerman, J. W. (1991) Protein kinase C and cyclic AMP regulate reversible exposure of binding sites for fibrinogen on the glycoprotein IIB-IIIA complex of human platelets. Biochem. J. 273, 115-120. https://doi.org/10.1042/bj2730115
  41. Weiss, H. J., Tschopp, T. B., Rogers, J. and Brand, H. (1974) Studies of platelet 5-hydroxytryptamine (serotonin) in storage pool disease and albinism. J. Clin. Invest. 54, 421-433. https://doi.org/10.1172/JCI107778
  42. Wong, Y. Y., Moon, A., Duffin, R., Barthet-Barateig, A., Meijer, H. A., Clemens, M. J. and de Moor, C. H. (2010) Cordycepin inhibits protein synthesis and cell adhesion through effects on signal transduction. J. Biol. Chem. 285, 2610-2621. https://doi.org/10.1074/jbc.M109.071159
  43. Yue, G. G., Lau, C. B., Fung, K. P., Leung, P. C., and Ko, W. H. (2008) Effects of Cordyceps sinensis, Cordyceps militaris and their isolated compounds on ion transport in Calu-3 human airway epithelial cells. J. Ethnopharmacol. 117, 92-101. https://doi.org/10.1016/j.jep.2008.01.030
  44. Zhang, J., Zhang, J., Shattil, S. J., Cunningham, M. C. and Rittenhouse, S. E. (1996) Phosphoinositide 3-kinase gamma and p85/ phosphoinositide 3-kinase in platelets. Relative activation by thrombin receptor or beta-phorbol myristate acetate and roles in promoting the ligand-binding function of alphaIIbbeta3 integrin. J. Biol. Chem. 271, 6265-6272. https://doi.org/10.1074/jbc.271.11.6265

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